Inhibitors of Viral Entry

The entry of viruses into target cells involves a complex series of sequential steps, with opportunities for inhibition at every stage. Entry inhibitors exert their biological properties by inhibiting protein—protein interactions either within the viral envelope (Env) glycoproteins or between viral Env and host-cell receptors. The nature of resistance to entry inhibitors also differs from compounds inhibiting enzymatic targets due to their different modes of action and the relative variability in Env sequences both temporally and between patients. Two drugs that target HIV-1 entry, enfuvirtide and maraviroc, are now licensed for treatment of HIV-1 infection. The efficacy of these drugs validates entry as a point of intervention in viral life cycles and, in the context of HIV treatment, contributes to the growing armamentarium of antivirals which, in multidrug combinations, can effectively inhibit viral replication and prevent disease progression.